Interleukin-4 (IL-4), previously known as B cell stimulating factor, or BSF-1, was originally characterized by its ability to stimulate the proliferation of B cells in response to low concentrations of antibodies directed to surface immunoglobulin. IL-4 has been shown to possess a far broader spectrum of biological activities, including growth co-stimulation of T cells, mast cells, granulocytes, megakaryocytes, and erythrocytes. In addition, IL-4 stimulates the proliferation of several IL-2- and IL-3-dependent cell lines, induces the expression of class II major histocompatibility complex molecules on resting B cells, and enhances the secretion of IgE and IgG1 isotypes by stimulated B cells. IL-4 is associated with a TH2-type immune response, being one of the cytokines secreted by TH2 cells.
Murine and human IL-4 have been identified and characterized, including cloning of IL-4 cDNAs and determination of the nucleotide and encoded amino acid sequences. See Yokota et al., 1986, Proc. Natl. Acad. Sci. USA 83:5894; Noma et al., 1986, Nature 319:640; Grabstein et al., 1986, J. Exp. Med. 163:1405; and U.S. Pat. No. 5,017,691.
IL-4 binds to particular cell surface receptors, which results in transduction of a biological signal to cells such as various immune effector cells. IL-4 receptors are described, and DNA and amino acid sequence information presented, in Mosley et al., 1989, Cell 59:335-48, (murine IL-4R); Idzerda et al., 1990, J. Exp. Med. 171:861-73, (human IL-4R); and U.S. Pat. No. 5,599,905. The IL-4 receptor described in these publications is sometimes referred to as IL-4R alpha.
Other proteins have been reported to be associated with IL-4R alpha on some cell types, and to be components of multi-subunit IL-4 receptor complexes. One such subunit is IL-2R gamma, also known as IL-2R gamma c. See the discussion of IL-4R complexes in Sato et al., 1994, Current Opinion in Cell Biology, 6:174-79. IL-4R alpha also has been reported to be a component of certain multi-subunit IL-13 receptor complexes. See Zurawski et al., 1995, J. Biol. Chem. 270:13869; de Vries, 1998, J. Allergy Clin. Immunol. 102:165; and Callard et al., 1996, Immunology Today, 17:108.
IL-4 has been implicated in a number of disorders, examples of which are allergy and asthma.